The overall goal of this application is to support the education and research endeavors of the investigator, who has the intention of developing a career as an independent investigator of observational epidemiologic research focused on age-related comorbidities (i.e. myocardial infarction [MI], end-stage renal disease [ESRD] and non-AIDS related cancers [cancer]) in HIV-infected individuals. To-date, the candidate has received excellent doctoral training in HIV and epidemiologic methods; she has begun focusing research interests on comorbidities among individuals aging with HIV infection. The career development award allows for five years of didactic and scientific training to establish a career as an independent research investigator via the following mechanisms:1) direct mentorship in research question generation, study design, statistical analysis, interpretation of findings, scientific communication and manuscript preparation from expert HIV epidemiologist Dr. Stephen Gange (mentor) and aging with HIV expert clinician and researcher Dr. Kelly Gebo (co-mentor) through weekly meetings, semi-annual goals evaluation, and productivity tracking using document sharing software; 2) consultation from Dr. Amy Justice, Principal Investigator (PI) of the Veterans Aging Cohort Study (VACS) and expert in aging with HIV clinician and epidemiologist, Dr. Richard Moore, PI of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and expert HIV clinician and researcher, and Dr. Cynthia Boyd, gerontologist and leader in research of multimorbidity in older adults; 3) obtaining formal instruction in aging epidemiology, the mechanism of aging in disease processes and causal inference methods at the Johns Hopkins Bloomberg School of Public Health (JHSPH); 4) implementing the proposed research in the data-rich environment of VACS and NA-ACCORD studies; 4) utilizing the resource-rich environments of the Statistics in Epidemiology (STATEPI) research group, and the Department of Epidemiology, JHSPH, and the Johns Hopkins School of Medicine (JHSOM). Immediate, short-term and longer-term career goals include increasing productivity to at least five publications and one oral presentation at a scientific conference each calendar year, successfully competing for R01 funding for studies investigating multimorbidity in aging HIV-infected individuals by 2016, and achieving a productive career as an independent research investigator, respectively. It is estimated =50% of people living with HIV in the US in 2015 will be aged =50 years. The overall aim of the proposed research is to challenge and expand upon paradigms in aging with HIV research by investigating three questions of clinical and public health significance: 1) Do HIV-infected individuals have a higher risk of comorbidities compared to sociodemographically similar HIV-uninfected individuals? 2) Are traditional or HIV- related risk factors driving the increased risk of comorbidities in HIV-infected individuals? 3) What is the impact of the timing of highly active antiretroviral therapy (HAART) initiation on the risk of comorbidities? These questions will be asked by investigating the following aims: Aim 1: To estimate the difference in risk of comorbidities in HIV-infected and similar -uninfected individuals in the US in clinical care, by age at comorbidity diagnosis. Aim 2: To determine the attributable fraction of traditional and HIV-related risk factors on comorbidities in HIV-infected individuals in clinical care in the US and Canada. Aim 3: To determine the risk of first comorbid event after HAART initiation by CD4 count at HAART initiation in HIV-infected individuals in clinical care in the US and Canada. The Veteran's Aging Cohort Study (VACS) is a longitudinal, multisite observational study of >100,000 HIV- infected and similar -uninfected patients with the aim of evaluating age-related comorbidites in HIV-infected individuals, making it an ideal cohort to investigate Aim 1. Although the generalizability of the findings from this predominantly male cohort may be restricted, the HIV-infected and -uninfected individuals were matched by age, race and ethnicity, sex and geographical location, ensuring strong internal validity to investigate the HIV effect. The NA-ACCORD is a longitudinal, multisite observational study of HIV-infected individuals, enrolling >115,000 HIV-infected participants with data collection efforts underway for MI, ESRD, and cancer events. This collaboration of cohorts is uniquely positioned to address Aims 2 and 3 with a sample size large enough to capture an adequate number of comorbid events. The 1) data-rich environments of the VACS and the NA- ACCORD, 2) resource-rich environments of STATEPI, the Department of Epidemiology and the JHSOM, and 3) assembled multidisciplinary team of mentors and consultants allows for the investigation of these aims, that challenge and expand upon current paradigms in aging with HIV, to serve as the candidate's foundation for a successful career as an independent research investigator.